The dopamine transporter is a key target or "receptor" for cocaine that mediates its addicting properties. Therefore, understanding the factors which control the levels of dopamine transporter in brain is essential for understanding mechanisms of drug addiction. This project plans to develop a method to measure the synthesis rate and degradation rate of the dopamine transporter, and the serotonin transporter as well. The serotonin transporter is important because it is a target or receptor for antidepressant drugs. Substantial progress has been made in that the serotonin transporter turnover has been measured and its half-life is 3.4 days. We are in the process of determining the same factors for the dopamine transporter. FUNDING NIH / DA11178 $141,199 08/01/97 - 06/30/00 PUBLICATIONS Boja, J.W., Carroll, F.I., Vaughan, R.A., Kopajtic, T. and Kuhar, M.J. Multiple binding sites for [125I]RTI-121 and other cocaine analogs in rat frontal cerebral cortex. Synapse 30:9-17, 1998. Ding, Y.-S., Molina, P.E., Fowler, J.S., Logan, J., Volkow, N.D., Kuhar, M.J. and Carroll, F.I. Comparative studies of epibatidine derivatives [18F]NFEP and [18F]N-methyl-NFEP Kinetics, nicotine, effect, and toxicity. Nucl. Med. Biol. 25:139-148, 1999. Kuhar, M. Neurotransmitter transporters are NOT in the Synapse? Presented at INABIS '98 - 5th Internet World Congress on Biomedical Sciences at McMaster University, Canada, December 7-16th. Invited Symposium. Kuhar, M.J., Vaughan, R., Uhl, G., Cerruti, C., Revay, R., Freed, C., Nirenburg, M. and Pickel, V. Localization of dopamine transporter protein by microscopic histochemistry. Adv. Pharmacol. 42:168-170, 1998. Vaughan, R.A., Huff, R.A., Uhl, G.R. and Kuhar, M.J. Phosphorylation of dopamine transporters and rapid adaptation to cocaine, in Goldstein, D.S., Eisenhofer, G., and McCarty, R. (Eds.) Catecholamines Bridging Basic Science with Clinical Medicine, Academic Press, San Diego, pp. 1042-, 1998. P51RR00165-38 1/1/98 - 12/31/98 Yerkes Regional Primate Research Center